Key result
Dabigatran showed consistent efficacy against stroke compared with warfarin across renal function subgroups (interaction P>0.1), with lower major bleeding in patients with GFR ≥80 mL/min.
Why the study?
Does dabigatran reduce stroke or systemic embolism and major bleeding compared to warfarin in patients with nonvalvular atrial fibrillation across different levels of renal function?
RCT (n=17,951)
Does dabigatran reduce stroke or systemic embolism and major bleeding compared to warfarin in patients with nonvalvular atrial fibrillation across different levels of renal function?
p-value: p=>0.1
Dabigatran maintains its efficacy over warfarin for stroke prevention in atrial fibrillation regardless of renal function, but its relative safety benefit for major bleeding is greater in patients with normal or mildly impaired renal function.
Supports preferring dabigatran over warfarin in AF with GFR ≥80 mL/min for lower bleeding; confirms consistent stroke prevention across renal subgroups.
BACKGROUND: Renal impairment increases the risk of stroke and bleeding in patients with atrial fibrillation. In the Randomized Evaluation of Long-Term Anticoagulant Therapy (RELY) trial, dabigatran, with ≈80% renal elimination, displayed superiority over warfarin for prevention of stroke and systemic embolism in the 150-mg dose and significantly less major bleeding in the 110-mg dose in 18 113 patients with nonvalvular atrial fibrillation. This prespecified study investigated these outcomes in relation to renal function. METHODS AND RESULTS: Glomerular filtration rate was estimated with the Cockcroft-Gault, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Modification of Diet in Renal Disease (MDRD) equations in all randomized patients with available creatinine at baseline (n=17 951), and cystatin C-based glomerular filtration rate was estimated in a subpopulation with measurements available (n=6190). A glomerular filtration rate ≥80, 50 to <80, and <50 mL/min was estimated in 32.6%, 47.6%, and 19.8% and in 21.6%, 59.6%, and 18.8% of patients based on Cockcroft-Gault and CKD-EPI, respectively. Rates of stroke or systemic embolism, major bleeding, and all-cause mortality increased as renal function decreased. The rates of stroke or systemic embolism were lower with dabigatran 150 mg and similar with 110 mg twice daily compared with warfarin, without significant heterogeneity in subgroups defined by renal function (interaction P>0.1 for all). For the outcome of major bleeding, there were significant interactions between treatment and renal function according to CKD-EPI and MDRD equations, respectively (P<0.05). The relative reduction in major bleeding with either dabigatran dose compared with warfarin was greater in patients with glomerular filtration rate ≥80 mL/min. CONCLUSIONS: The efficacy of both dosages of dabigatran was consistent with the overall trial irrespective of renal function. However, with the CKD-EPI and MDRD equations, both dabigatran dosages displayed significantly lower rates of major bleeding in patients with glomerular filtration rate ≥80 mL/min. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00262600.
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Hijazi et al. (2013) conducted an RCT in nonvalvular atrial fibrillation (n=17,951). dabigatran vs. warfarin was evaluated on stroke or systemic embolism (p=>0.1). Dabigatran showed consistent efficacy against stroke compared with warfarin across renal function subgroups (interaction P>0.1), with lower major bleeding in patients with GFR ≥80 mL/min.
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